Variation in Inflammatory/Regulatory Cytokines in Secondary, Tertiary, and Quaternary Challenges with Dengue Virus

Sierra, Beatríz; Pérez, Ana B.; Álvarez, Mayling; Garcı́a, Gissel; Vogt, Katrin; Aguirre, Eglys; Schmolke, Kathrin; Volk, Hans‐Dieter; Guzmán, María G.

doi:10.4269/ajtmh.2012.11-0531

Cited by 19 publications

(13 citation statements)

References 66 publications

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“…High concentrations of IL-6 were found in dengue patients in our study, and this is consistent with most studies [ 31 , 42 , 49 – 51 ]. IL-6 has been associated with the increment of vascular permeability, plasma leakage, pleural effusion, and ascites [ 41 , 51 , 52 ]. IL-6 induces leukocyte recruitment, local inflammation, and damage to endothelial cells.…”

Section: Discussionsupporting

confidence: 93%

IL-10 and socs3 Are Predictive Biomarkers of Dengue Hemorrhagic Fever

Flores-Mendoza

Estrada-Jiménez

Sedeño-Monge

et al. 2017

Mediators of Inflammation

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Background Cytokines play important roles in the physiopathology of dengue infection; therefore, the suppressors of cytokine signaling (socs) that control the type and timing of cytokine functions could be involved in the origin of immune alterations in dengue. Objective To explore the association of cytokine and socs levels with disease severity in dengue patients. Methods Blood samples of 48 patients with confirmed dengue infection were analyzed. Amounts of interleukins IL-2, IL-4, IL-6, and IL-10, interferon- (IFN-) γ, and tumor necrosis factor- (TNF-) α were quantified by flow cytometry, and the relative expression of socs1 and socs3 mRNA was quantified by real-time RT-PCR. Results Increased levels of IL-10 and socs3 and lower expression of socs1 were found in patients with dengue hemorrhagic fever (DHF) with respect to those with dengue fever (DF) (p < 0.05). Negative correlations were found between socs1 and both IL-10 and socs3 (p < 0.01). The cutoff values of socs3 (>199.8-fold), socs1 (<1.94-fold), and IL-10 (>134 pg/ml) have the highest sensitivity and specificity to discriminate between DF and DHF. Conclusion Simultaneous changes in IL-10 and socs1/socs3 could be used as prognostic biomarkers of dengue severity.

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Section: Discussionsupporting

confidence: 93%

IL-10 and socs3 Are Predictive Biomarkers of Dengue Hemorrhagic Fever

Flores-Mendoza

Estrada-Jiménez

Sedeño-Monge

et al. 2017

Mediators of Inflammation

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“…Cytokine levels in primary and secondary DENV infections have been compared, and the differences are not enough to indicate that DHF pathogenesis is completely attributable to increased cytokine expression during secondary DENV infection, despite their importance in endothelial damage and inflammatory responses ( Chakravarti & Kumaria 2006 , Priyadarshini et al 2010) . There is also evidence to suggest that the cytokine expression levels decreased in subsequent DENV infections ( Sierra et al 2012) . In this study, only primary DENV infections were considered, and the higher levels of most of the analysed cytokines were observed in samples from DHF patients who were infected with DENV2.…”

Section: Discussionmentioning

confidence: 99%

Primary dengue virus infections induce differential cytokine production in Mexican patients

Hernández

Puerta-Guardo

Aguilar

et al. 2016

Mem. Inst. Oswaldo Cruz

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Severe dengue pathogenesis is not fully understood, but high levels of proinflammatory cytokines have been associated with dengue disease severity. In this study, the cytokine levels in 171 sera from Mexican patients with primary dengue fever (DF) and dengue haemorrhagic fever (DHF) from dengue virus (DENV) 1 (n = 116) or 2 (n = 55) were compared. DF and DHF were defined according to the patient’s clinical condition, the primary infections as indicated by IgG enzymatic immunoassay negative results, and the infecting serotype as assessed by real-time reverse transcription-polymerase chain reaction. Samples were analysed for circulating levels of interleukin (IL)-12p70, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, IL-6, and IL-8 using a commercial cytometric bead array. Significantly higher IFN-γ levels were found in patients with DHF than those with DF. However, significantly higher IL-12p70, TNF-α, and IL-6 levels were associated with DHF only in patients who were infected with DENV2 but not with DENV1. Moreover, patients with DF who were infected with DENV1 showed higher levels of IL-12p70, TNF-α, and IL-6 than patients with DHF early after-fever onset. The IL-8 levels were similar in all cases regardless of the clinical condition or infection serotype. These results suggest that the association between high proinflammatory cytokine levels and dengue disease severity does not always stand, and it once again highlights the complex nature of DHF pathogenesis.

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“…Further work has demonstrated the T cell response was most marked to NS3 protein, with high cytokine and low CD107a (a marker of cell degranulation) predominating 54 . The resulting cytokine release, particularly tumor necrosis factor alpha and other vasoactive mediators, may then play a role in the increase in capillary permeability seen in severe dengue 55 – 57 .…”

Section: Pathogenesis Of Severe Diseasementioning

confidence: 99%

Recent advances in understanding dengue

2016

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Dengue is an emerging threat to billions of people worldwide. In the last 20 years, the incidence has increased four-fold and this trend appears to be continuing. Caused by one of four viral serotypes, dengue can present as a wide range of clinical phenotypes with the severe end of the spectrum being defined by a syndrome of capillary leak, coagulopathy, and organ impairment. The pathogenesis of severe disease is thought to be in part immune mediated, but the exact mechanisms remain to be defined. The current treatment of dengue relies on supportive measures with no licensed therapeutics available to date. There have been recent advances in our understanding of a number of areas of dengue research, of which the following will be discussed in this review: the drivers behind the global dengue pandemic, viral structure and epitope binding, risk factors for severe disease and its pathogenesis, as well as the findings of recent clinical trials including therapeutics and vaccines. We conclude with current and future dengue control measures and key areas for future research.

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Variation in Inflammatory/Regulatory Cytokines in Secondary, Tertiary, and Quaternary Challenges with Dengue Virus

Cited by 19 publications

References 66 publications

IL-10 and socs3 Are Predictive Biomarkers of Dengue Hemorrhagic Fever

IL-10 and socs3 Are Predictive Biomarkers of Dengue Hemorrhagic Fever

Primary dengue virus infections induce differential cytokine production in Mexican patients

Recent advances in understanding dengue

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